Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence indicates that relugolix-estradiol-norethisterone acetate is more effective than placebo for reducing heavy menstrual bleeding, with 73% and 71% of participants achieving the primary outcome in the LIBERTY trials compared to 19% and 15% in the placebo groups. However, the treatment has only been indirectly compared with GnRH agonists, suggesting comparable efficacy but with significant uncertainty in the results.
Cost effectiveness
The cost-effectiveness estimates for relugolix-estradiol-norethisterone acetate are generally within the acceptable range for Healthcare resources, with a base-case ICER of less than £20,000 per QALY gained. The committee acknowledged potential uncaptured QALY benefits that could further support its cost-effectiveness.
Quality of life
The treatment is associated with improvements in quality of life, particularly in reducing heavy menstrual bleeding, which is a significant concern for patients. The evidence from the LIBERTY trials indicates that the treatment leads to a statistically significant improvement in UFS-QoL scores compared to placebo, suggesting a moderate benefit in HRQoL.
Supporting Domains
Safety and Adverse Effects
Relugolix-estradiol-norethisterone acetate has a favorable safety profile, with adverse events reported at similar rates to placebo in the LIBERTY trials. The most common adverse events were mild to moderate, and no deaths were reported, indicating a very good tolerability.
Comparator Selection
The treatment was compared with GnRH agonists, which are considered the most relevant comparators. However, the absence of direct head-to-head trials introduces uncertainty, as the evidence relies on indirect comparisons, which may not fully capture the comparative effectiveness.
Patient Population and Subgroups
The trials included a representative population of premenopausal women aged 18 to 50 with heavy menstrual bleeding due to uterine fibroids. The inclusion criteria were well-defined, and while there are some limitations, the core population is adequately covered.
Care Pathway Integration
Relugolix-estradiol-norethisterone acetate can be easily integrated into existing care pathways as an oral treatment option, which is a significant advantage over injectable GnRH agonists. This facilitates patient adherence and reduces the need for clinic visits.
Resource Use and Cost Implications
The treatment is expected to have a manageable budget impact, with potential cost savings associated with reduced surgical interventions. The economic model suggests that the treatment is resource-efficient, although there are uncertainties regarding long-term costs.
Evidence Quality and Robustness
The evidence is based on two phase 3 RCTs, which provide a strong foundation for the clinical claims. However, there are some methodological concerns regarding the indirect comparisons and the use of different measurement techniques for menstrual blood loss.
Uncertainty, Sensitivity, and Broader Impacts
There is notable uncertainty regarding the indirect treatment comparisons and the generalizability of the results. The committee expressed concerns about the robustness of the economic model and the potential impact of discontinuation rates on the overall assessment.
